The direct injection of morphine into the midbrain periaqueductal gray (PAG) has been consistently shown to elicit analgesia in experimental animals. The exquisite sensitivity of this brain site and its reported high concentration of opiate receptors provide considerable evidence favoring a major role for the PAG in the production of opiate analgesia. The involvement of brain catecholamines (norepinephrine and dopamine) in the actions of opiate analgesics has also been implicated by a number of previous studies. The locus coeruleus and substantia nigra, points of origin of the brain norepinephrine and dopamine pathways, also contain relatively high amounts of opiate receptors and the peripheral administration of opiates has been consistently shown to produce increases in brain catechoamine turnover. However, the brain structures involved in mediating these increases in turnover and the relationship of this effect to the analgesia actions of opiates are unclear. The relative importance of the contributions of norepinephrine and dopamine to the analgesic action of opiates is also unknown. The objective of this research is to more clearly define the neuronatomical and neurochemical aspects of opiate analgesia by measuring the analgesia effects and regional changes in brain catecholamine turnover produced by intracerebral injections of opiates. A sensitive indication of turnover change will be provided by measurements of the major catecholamine metabolites, 3-methoxy-4-hydroxyphenylethyleneglyco sulfate, 3,4-dihydroxyphenylacetic acid and homovanillic acid in those areas of the brain which are innervated by axonal projections of the catecholamine pathways (cortex, hypothalamus, limbic system and corpus striatum). Analgesia indicated by the rat tail flick procedure and regional changes in catecholamine metabolites will be measured in the same animals following injections of opiates into the PAG, locus coeruleus and/or substantia nigra. Correlations between the analgesic effects and changes in turnover will be evaluated and the relationships obtained will provide a greatly enhanced understanding of the mechanisms of action of opiate analgesics.